BCL-2 family protein, BAD is down-regulated in breast cancer and inhibits cell invasion
| Autor: | Jay Wimalasena, Mugdha Sukhthankar, Paul A. Wade, Arnold M. Saxton, Romaine I. Fernando, Maria Cekanova, Christine C. Malone, Richard G. Pestell, Jirayus Woraratphoka, Robert M. Donnell, Columba de la Parra, Suranganie Dharmawardhane, Nalin Siriwardhana, Seung Joon Baek, Anders Ström |
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| Rok vydání: | 2015 |
| Předmět: |
MAPK/ERK pathway
Epithelial-Mesenchymal Transition MMP10 Blotting Western Down-Regulation Enzyme-Linked Immunosorbent Assay Biology Real-Time Polymerase Chain Reaction Article Metastasis Immunoenzyme Techniques Cyclin D1 Breast cancer Cell Movement Tumor Cells Cultured medicine Humans RNA Messenger Phosphorylation Protein kinase B beta Catenin Cell Proliferation Reverse Transcriptase Polymerase Chain Reaction Bcl-2 family Cell Biology Flow Cytometry medicine.disease Molecular biology STAT Transcription Factors MCF-7 Cells Female bcl-Associated Death Protein Signal transduction Proto-Oncogene Proteins c-akt |
| Zdroj: | Experimental Cell Research. 331:1-10 |
| ISSN: | 0014-4827 |
| Popis: | We have previously demonstrated that the anti-apoptotic protein BAD is expressed in normal human breast tissue and shown that BAD inhibits expression of cyclin D1 to delay cell-cycle progression in breast cancer cells. Herein, expression of proteins in breast tissues was studied by immunohistochemistry and results were analyzed statistically to obtain semi-quantitative data. Biochemical and functional changes in BAD-overexpressing MCF7 breast cancer cells were evaluated using PCR, reporter assays, western blotting, ELISA and extracellular matrix invasion assays. Compared to normal tissues, Grade II breast cancers expressed low total/phosphorylated forms of BAD in both cytoplasmic and nuclear compartments. BAD overexpression decreased the expression of β-catenin, Sp1, and phosphorylation of STATs. BAD inhibited Ras/MEK/ERK and JNK signaling pathways, without affecting the p38 signaling pathway. Expression of the metastasis-related proteins, MMP10, VEGF, SNAIL, CXCR4, E-cadherin and TlMP2 was regulated by BAD with concomitant inhibition of extracellular matrix invasion. Inhibition of BAD by siRNA increased invasion and Akt/p-Akt levels. Clinical data and the results herein suggest that in addition to the effect on apoptosis, BAD conveys anti-metastatic effects and is a valuable prognostic marker in breast cancer. |
| Databáze: | OpenAIRE |
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